2. Academic Validation
  3. Design and synthesis of 4-morpholino-6-(1,2,3,6-tetrahydropyridin-4-yl)-N-(3,4,5-trimethoxyphenyl)-1,3,5-triazin-2-amine analogues as tubulin polymerization inhibitors

Design and synthesis of 4-morpholino-6-(1,2,3,6-tetrahydropyridin-4-yl)-N-(3,4,5-trimethoxyphenyl)-1,3,5-triazin-2-amine analogues as tubulin polymerization inhibitors

  • Bioorg Med Chem Lett. 2017 Aug 15;27(16):3794-3801. doi: 10.1016/j.bmcl.2017.06.060.
Suresh Narva 1,  Surendar Chitti 1,  Suresh Amaroju 1,  Debanjan Bhattacharjee 2,  Bala Bhaskara Rao 2,  Nishant Jain 2,  Mallika Alvala 3,  Kondapalli Venkata Gowri Chandra Sekhar 4
Affiliations

Affiliations

  • 1 Department of Chemistry, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, Telangana, India.
  • 2 Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, Telangana, India.
  • 3 National Institute of Pharmaceutical Education and Research-Hyderabad, Hyderabad 500037, Telangana, India.
  • 4 Department of Chemistry, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, Telangana, India. Electronic address: kvgcs.bits@gmail.com.
PMID: 28684120 DOI: 10.1016/j.bmcl.2017.06.060
Abstract

A series of thirty-seven 1,3,5-triazine analogues have been synthesized, characterized and evaluated for their antiproliferative activity against a panel of four different human Cancer cell lines such as HeLa, HepG2, A549 and MCF-7. Most of the 1,3,5-triazine analogues exhibited promising antiproliferative activity against tested Cancer cell lines. Among all the synthesized compounds, 8j showed potent activity against the Cancer cell lines such as HeLa, HepG2, A549 and MCF-7 with IC50 12.3±0.8, 9.6±0.4, 10.5±1.0 and 11.7±0.5μM respectively. 8j was taken up for elaborate biological studies and the cells in the cell cycle were arrested in G2/M phase. In addition, 8j was examined for its effect on the microtubule system with a tubulin polymerization assay, immunofluorescence. 8j showed remarkable inhibition of tubulin polymerization. Molecular docking studies were also carried out to understand the binding pattern. The studies suggested that 8jhas a good binding affinity of -7.949 towards nocodazole binding site of tubulin while nocodazole has -7.462.

Keywords

1,3,5-Triazine; Antiproliferative activity; Molecular docking study; Morpholine; Tubulin polymerization.

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